Mechanisms of programmed cell death signaling in hair cells and support cells post-electrode insertion trauma. (April 2015)

• Record Type: Journal Article
• Authors: Eshraghi, Adrien A; Lang, Dustin M; Roell, Jonathan; Van De Water, Thomas R; Garnham, Carolyn; Rodrigues, Helio; Guardiola, Mateo; Gupta, Chhavi; Mittal, Jeenu
• Is Part Of: Acta oto-laryngologica. Volume 135:Number 4(2015)
• Page Start: 328
• Page End: 334
• Publication Date: 2015-04
• Subjects: cochlear implant -- electrode-induced trauma -- hair cell loss -- electrode insertion trauma grading system; Otolaryngology -- Periodicals; Ear -- Diseases -- Periodicals; Throat -- Diseases -- Periodicals; Otolaryngology -- Electronic Resources; Otorhinolaryngologic Diseases; 617.8
• DOI: 10.3109/00016489.2015.1012276
• Languages: English
• ISSNs: 0001-6489

Abstract

Abstract: Conclusion: Programmed cell death (PCD) initially starts in the support cells (SCs) after electrode insertion trauma (EIT), followed by PCD in hair cells (HCs). Activation of caspase-3 was observed only in SCs. Protecting both SCs and HCs with selective otoprotective drugs at an early stage post implantation may help to preserve residual hearing. Objectives: Cochlear implant EIT can initiate sensory cell losses via necrosis and PCD within the organ of Corti, which can lead to a loss of residual hearing. PCD appears to be a major factor in HC loss post-EIT. The current study aimed to: (1) determine the onset of PCD in both SCs and HCs within the traumatized organ of Corti; and (2) identify the molecular mechanisms active within the HCs and SCs that are undergoing PCD. Methods: Adult guinea pigs were assigned to one of two groups: (1) EIT and (2) unoperated contralateral ears as controls. Immunostaining of dissected organ of Corti surface preparations for phosphorylated-Jun, cleaved caspase-3, and 4-hydroxy-2, 3-nonenal (HNE) were performed at 6, 12, and 24 h post-EIT and for contralateral control ears. Results: At 6 h post-EIT the SCs immunolabeled for the presence of phosphorylated-Jun and activated caspase-3. Phosphorylated p-Jun labeling was observed at 12 h in both the HCs and SCs of middle and basal cochlear turns. Cleaved caspase-3 was not observed in HCs of any cochlear turn at up to 24 h post-EIT. Lipid peroxidation (HNE immunostaining) was first observed at 12 h post-EIT in both the HCs and SCs of the basal turn, and reached the apical turn by 24 h post-EIT.